C L I N I C A L A N D LA B O R A T O R Y I N V E S T I G A T I O N S                DOI 10.1111/j.1365-2133.2005.06562.xHu...
962 HPV-associated eccrine epidermoid cyst, K. Egawa et al.infection from injuries as they do occasionally develop afterin...
HPV-associated eccrine epidermoid cyst, K. Egawa et al. 963                                                               ...
964 HPV-associated eccrine epidermoid cyst, K. Egawa et al.                                                               ...
HPV-associated eccrine epidermoid cyst, K. Egawa et al. 965                                                               ...
966 HPV-associated eccrine epidermoid cyst, K. Egawa et al.surface (ridged warts).16,17 Thus, the clinical morphology of  ...
HPV-associated eccrine epidermoid cyst, K. Egawa et al. 967 9 Ohnishi T, Watanabe S. Immunohistochemical observation of cy...
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Cisto metap ecrina hpv

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Cisto metap ecrina hpv

  1. 1. C L I N I C A L A N D LA B O R A T O R Y I N V E S T I G A T I O N S DOI 10.1111/j.1365-2133.2005.06562.xHuman papillomavirus-associated plantar epidermoid cystrelated to epidermoid metaplasia of the eccrine ductepithelium: a combined histological,immunohistochemical, DNA–DNA in situ hybridization andthree-dimensional reconstruction analysisK. Egawa, N. Egawa* and Y. Honda Departments of Dermatology and  Surgical Pathology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-0811, Japan*Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan SummaryCorrespondence Background We recently proposed that certain palmoplantar epidermoid cysts mayKiyofumi Egawa. be related to eccrine ducts and that human papillomavirus (HPV) 60 may play aE-mail: kuroibo@kaiju.medic.kumamoto-u.ac.jp role in their pathomechanism. However, the origin of palmoplantar epidermoid cysts is still controversial.Accepted for publication9 October 2004 Objectives To examine the contribution of eccrine ducts and HPV 60 in the devel- opment of epidermoid cysts.Key words: Methods Five epidermoid cysts and four ridged warts that had developed on theeccrine duct, epidermoid cyst, human soles of a patient were studied histologically, immunohistochemically and bypapillomavirus 60, inclusion cyst, metaplasia DNA–DNA in situ hybridization. Using serial sections obtained from its entire body, a three-dimensional reconstruction (3DR) analysis was performed on theConflicts of interest:None declared. smallest cyst to analyse the relationship between the epidermoid cyst, eccrine duct and the overlying epidermis. Results Histological and DNA–DNA in situ hybridization analyses demonstrated both homogeneous intracytoplasmic inclusion bodies pathognomonic for HPV 60 infection and HPV 60 DNA sequences not only in all of the epidermoid cysts and ridged warts but also in the acrosyringeal portion of an eccrine duct, with the dermal portion of which the smallest cyst had been revealed to connect by 3DR analysis. However, immunohistochemical analyses using antibodies against human carcinoembryonic antigen (CEA), involucrin and several cytokeratins (CKs) revealed that the immunoreactivity of the cyst was not identical to that of the eccrine dermal duct but was identical to that of suprabasal layers of the epidermis. Conclusions It was clearly demonstrated that an HPV 60-associated epidermoid cyst with immunoreactivities for CEA, involucrin and CKs which were identical to those of the epidermis connected with the eccrine dermal duct, supporting the idea that certain palmoplantar epidermoid cysts may develop following the epi- dermoid metaplasia of eccrine ducts with HPV 60 infection.Epidermoid cysts of palmoplantar location (palmoplantar epi- epidermoid cysts, with or without infection by human papil-dermoid cysts) have been described as being caused by lomavirus (HPV) 60,5 and therefore proposed the alternativeimplantation of epidermal fragments into the dermis as a pathogenic hypothesis that certain palmoplantar epidermoidresult of a penetrating or blunt injury.1 However, this assump- cysts may develop from eccrine ducts and that HPV 60 maytion has been questioned, and the necessity of a search for a play a role in this development. However, on the basis of themore common aetiology has been stressed.2 previous results,3–5 it is still likely that such epidermoid cysts We previously observed3,4 that eccrine sweat ducts were can develop as a result of the implantation of epidermal frag-frequently found in and ⁄or connecting with palmoplantar ments that contain eccrine ducts with or without HPV 60Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967 961
  2. 2. 962 HPV-associated eccrine epidermoid cyst, K. Egawa et al.infection from injuries as they do occasionally develop afterinjuries3,6 and are mainly located beneath the weight-bearingareas of the foot, i.e. the balls and heels.7 Indeed, Abe et al.8 and Ohnishi and Watanabe9 questionedthe hypothesis of an ‘eccrine duct origin of the epidermoidcyst’ on the basis of the immunoreactivities of several cyto-keratins (CKs) which were not identical to those of sweatglands and ducts but were identical to those of suprabasallayers of the epidermis in plantar epidermoid cysts with HPVinfection. However, Egawa et al.10 proposed the idea that such a CKprofile in HPV-associated palmoplantar epidermoid cysts mightbe a reflection of the epidermoid metaplasia of the eccrineduct epithelium in the process of cyst formation in the eccrineducts, as it was revealed that the CK profile of cholesteatomas,which are histologically defined as epidermoid cysts develop-ing in the middle ear,11 cannot be used as a variable to decidewhether the origin of epidermoid cysts is epidermal or meta-plastic.12 Thus, the origin of palmoplantar epidermoid cysts isstill controversial. Three-dimensional reconstruction (3DR) analysis from serialsections is now a powerful tool for increasing our comprehen-sion of the relationships among structural components, for theindication of the connections between components, and forrevealing the distribution of components.13–15 In the presentstudy, using serial sections obtained from the entire body ofan epidermoid cyst, we attempted 3DR analysis to demon- Fig 1. Three subcutaneous nodules (solid arrows) and two ridgedstrate the fine structure of an HPV 60-associated epidermoid warts (open arrows) on the left sole.cyst of eccrine duct origin, in combination with histological,immunohistochemical and DNA–DNA in situ hybridizationanalyses. excised specimens were fixed in 10% formalin, and proc- essed with an automatic processor.Materials and methods HistopathologyPatient Four-micrometre thick sections were obtained using a micro-A 21-year-old Japanese woman presented to Kumamoto Uni- tome from all of the biopsy specimens, stained with haema-versity Hospital in April 1995, with several subcutaneous nod- toxylin and eosin (H&E), and examined microscopicallyules and warts on the soles of her feet. She first noticed (Figs 2 and 3). From the smallest cyst, gross serial sectionsseveral miliary-sized asymptomatic nodules on her soles were obtained from its entire body, and all sections were3 months before presentation and 1 year after having had sev- numbered in the order of sectioning, from one side to theeral plantar warts treated with cryotherapy, although she could other. Fifty serial sections were obtained from each of thenot say whether or not the nodules developed in the same other cysts. Every alternate section was stained with H&E forpositions as the treated plantar warts. The nodules had gradu- histological analysis (Fig. 3), whereas the remaining sectionsally enlarged and had come to cause tenderness during the were used for further examinations such as immunohisto-previous 3 months. chemical and DNA–DNA in situ hybridization analyses. At the time of her first visit, examination showed threesubcutaneous nodules of 5–8 mm diameter and two small Processing of histological and immunohistochemical dataflat warty lesions with clinical features of ridged warts16,17 for computer analysison the left sole (Fig. 1) and one nodule of 7 mm diameteron the right sole. Her health was otherwise good. After Using photomicrographs of histopathological and immunohis-informed consent was obtained, all the lesions were tochemically stained sections (Fig. 4a), we made montages byremoved successfully by scalpel under local anaesthesia. tracing the outlines of the histological ductal structures expres-However, about 6 months later, a further subcutaneous sing carcinoembryonic antigen (CEA) in serial sections in red,nodule of similar size appeared on the left sole, with two and those of the cyst wall and the overlying epidermis in blueridged warts. They were also removed by scalpel. The (Fig. 4b). Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967
  3. 3. HPV-associated eccrine epidermoid cyst, K. Egawa et al. 963 (Fig. 4d). The three-dimensional images were rotated along various axes to analyse the relationship between the cyst, eccrine ducts and the overlying epidermis. Immunohistochemistry An immunohistochemical procedure for human CEA,3,4,15,18 CKs8,9,19 and involucrin20 was performed on paraffin-embed- ded sections by the avidin–biotin–peroxidase complex (ABC) method,21 utilizing a Vectastain ABC kit (Vector Laboratories, Burlingame, CA, U.S.A.). A polyclonal antibody to human CEA (Dako, Glostrup, Denmark) and monoclonal antibodies to var- ious CKs (OV-TL 12 ⁄30, RCK108 and AE1 ⁄AE3, Dako; LL002, Biomeda, Foster City, CA, U.S.A.; and CAM5.2, Becton Dickin- son, San Jose, CA, U.S.A.) and involucrin (Novocastra, New-Fig 2. Histological features of a ridged wart. Vacuolar structures are castle-upon-Tyne, U.K.) were used as primary antibodiesseen in the thickened horny layer and homogeneous intracytoplasmic (Table 1). In the case of CKs, the procedure was performedinclusion bodies are seen in the granular and upper spinous cell layers with or without proteinase K predigestion or autoclave heatingof the acanthotic epidermis. A tiny keratinous cyst is seen just beneath for antigen retrieval as described previously.22 Negative con-the acanthotic epidermis (arrow). trols for immunostaining were performed by substituting the primary antibodies with phosphate-buffered saline or nonim- mune mouse or rabbit IgG.Three-dimensional reconstruction analysisAn image scanner (IX-4025; Canon, Tokyo, Japan) and a per- DNA–DNA in situ hybridizationsonal computer (Apple Macintosh 8500) were used in the3DR imaging. Montages of the serial sections obtained from HPV 60 DNA sequences were detected in formalin-fixed, paraf-the entire body of the epidermoid cyst were displayed on a fin-embedded tissue sections using the DNA–DNA in situ hybrid-television monitor (Multiscan 17s; Sony, Tokyo, Japan). The ization method as described previously.23,24 Hybridization wasoutlines of the cysts and the eccrine ducts were digitized and performed at 37 °C for 16 h using digoxigenin-labelled HPVstored on the computer to make a wire-frame of these in vivo 60 complete genome DNA which we had previously clonedstructures (Fig. 4c). Based on the wire-frame, three-dimen- from a plantar epidermoid cyst.3 The hybridization mixturesional images of the structures were reconstructed using an consisted of 10% dextran sulphate, 2 · saline sodium citrateimage analysis program (Specular Infini-D; Specular, Amherst, (0Æ3% sodium chloride, 0Æ03 mol L)1 sodium citrate, pH 7Æ0),MA, U.S.A.) and were displayed on the television monitor 400 lg mL)1 sheared herring sperm DNA (Sigma, St Louis,Fig 3. Representative histological picturesselected from the serial sections obtainedfrom the entire body of an epidermoidcyst. Section numbers appear at the lowerleft corner of each picture. Varyinghistological features coming from ahypertrophied eccrine dermal duct (no.200, inset) connecting the apical portionof the cyst with an acrosyringium in theoverlying epidermis are seen in the serialsections. The ecrine duct, appearing as aductal structure in the apical portion ofthe cyst wall (nos 180–190), goesupwards through the dermis to theacrosyringium (nos 200–210) andconnects with it in the overlyingepidermis (no. 220). The acrosyringium isextremely dilated in the horny layer (no.230).Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967
  4. 4. 964 HPV-associated eccrine epidermoid cyst, K. Egawa et al. Fig 4. Computer-based, three-dimensional reconstruction (3DR) analysis of a human papillomavirus 60-associated plantar epidermoid cyst. (a) Histological section (the same as Figure 3, no.190). (b) Tracing of the outline of the histological ductal structures expressing carcinoembryonic antigen (red) and of the cyst wall and overlying epidermis (blue). (c) A wire-frame of the epidermoid cyst generated by computer using a montage of tracings obtained from all the serial sections. (d) 3DR analysis visualizing the fine structure of the epidermoid cyst connecting with the eccrine dermal duct.Table 1 Immunohistochemical staining in a human papillomavirus (HPV) 60-associated plantar epidermoid cyst Normal eccrine gland Secretory Eccrine Antibody Specificity portion dermal duct Epidermis Cyst wall HD CEA +++ +++ – – ++ (IML) AE1 ⁄ AE3 CKs 10, 14–16, 19 ⁄ 1–8 +++ +++ +++ +++ +++ LL002 CK14 – ++ ++ (LL) ++ (OL) + (OL) OV-TL 12 ⁄ 30 CK7 +++ – – – – RCK108 CK19 + – – – – CAM5.2 CKs 8, 18 +++ – – – – Involucrin – – +++ (UL) +++ (IL) ++ (IL) HD, hypertrophied eccrine dermal duct with which the HPV 60-associated epidermoid cyst connected; CEA, carcinoembryonic antigen; CK, cytokeratin; IML, innermost layers; LL, lower layers; OL, outer layers; UL, upper layers; IL, inner layers; –, negative; +, weak; ++, moderate; +++, strong.MO, U.S.A.), 50% formamide and 2 lg mL)1 of probe DNA. (Figs 3 and 5c). The characteristic histological feature com-The digoxigenin-labelled probe was detected by the streptavi- monly seen in all the ridged warts and the epidermoid cystsdin-biotinylated polyalkaline phosphatase detection system was the presence of eosinophilic homogeneous intracyto-(DNA detection system; BRL, Gaithersburg, MD, U.S.A.). The plasmic inclusion bodies pathognomonic for HPV 60phaeochromes used were nitroblue tetrazolium and 5-bromo- infection3–7,16,17,24–27 in the granular and upper spinous cell4-chloro-3-indolylphosphate (Fig. 5). layers of the acanthotic epidermis of the ridged warts or in the inner cell layers of the cyst wall (Figs 2 and 5c). Vacuolar structures, also pathognomonic for HPV 60 infection,4,7 wereResults also seen both in the horny layer of the ridged warts and in keratinous material within the cyst cavity (Figs 2 and 5c).Histology In the serial sections obtained from the entire body of theIn the ridged warts, the epidermis was acanthotic with hyper- smallest cyst (Fig. 3), ductal structures coming from an eccrinekeratosis and partial hypergranulosis. In one lesion, a tiny dermal duct were seen between the apical portion of the cystkeratinous cyst was seen just beneath the acanthotic epidermis and an acrosyringium in the overlying epidermis in the dermis(Fig. 2). Epidermoid cysts were lined by stratified squamous that connects the two histological components (Fig. 3, nos.epithelium, showing keratinization of the epidermoid type 190–220). The eccrine dermal duct was hypertrophied with Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967
  5. 5. HPV-associated eccrine epidermoid cyst, K. Egawa et al. 965 duct but not the secretory portion. In contrast, OV-TL 12 ⁄30 (against CK7), RCK108 (against CK19) and CAM5.2 (against CKs 8 and 18) stained only the secretory portion. A monoclo- nal antibody against involucrin did not stain any portions of the normal eccrine sweat gland. Epidermis of the sole CEA was expressed only in the acrosyringeal epithelium in the epidermis. LL002 stained the lower cell layers; AE1 ⁄AE3 stained whole cell layers; OV-TL 12 ⁄30, RCK108 and CAM5.2 did not stain any cell layers; involucrin was expressed in the upper cell layers of the epidermis. Plantar epidermoid cyst CEA was not expressed in the cyst wall but was expressed in the acrosyringeal structures in the cyst cavity. LL002 stained the outer cell layers; AE1 ⁄AE3 stained whole cell layers; OV- TL 12 ⁄30, RCK108 and CAM5.2 did not stain any cell layers; involucrin was expressed in the inner cell layers of the cyst wall. Hypertrophied eccrine dermal duct with stratified squamous epithelium with which an epidermoid cyst connectedFig 5. Histological localization of human papillomavirus (HPV)60 DNA sequences. A high-power view of the same section The innermost cell layers of the stratified epithelium of the(a,c; haematoxylin and eosin) and a serial section (b,d; DNA–DNA hypertrophied eccrine dermal duct expressed CEA. Expressionin situ hybridization) of Figure 3, no. 230. Homogeneous of involucrin was also noted in the inner cell layers; LL002intracytoplasmic inclusion bodies (a,c) and HPV 60 DNA sequences stained the outer cell layers; AE1 ⁄AE3 stained whole cell(b,d) are seen in the acrosyringeal epithelium (a,b) as well as in the layers; OV-TL 12 ⁄30, RCK108 and CAM5.2 did not stain anycyst wall (c,d). cell layers of the duct. The results are summarized in Table 1.stratified squamous epithelium (Fig. 3, no. 200, inset); theacrosyringium was extremely dilated in the horny layer DNA–DNA in situ hybridization(Fig. 3, no. 230; Fig. 5a); and the homogeneous intracytoplas-mic inclusion bodies were seen in the acrosyringeal epithelium HPV 60 DNA sequences were detected in all the epidermoid(Fig. 5a) as well as in the epidermoid cyst (Fig. 5b). cysts and ridged warts. In the smallest epidermoid cyst ana- Ductal structures suggestive of eccrine ducts were observed lysed with 3DR, the DNA sequences were identified both inin three of the other four epidermoid cysts, using 50 serial the acrosyringeal portion of the eccrine duct (Fig. 5b) and insections obtained from each cyst. the cyst connecting with its dermal portion (Fig. 5d).Three-dimensional reconstruction analysis DiscussionThe analysis clearly demonstrated that the smallest epidermoid Implantation of epidermal fragments into the dermis has beencyst connected with the eccrine dermal duct (Fig. 4d). thought to be the main cause of palmoplantar epidermoid cysts.1 Although we have proposed an alternative pathogenic hypothesis that certain palmoplantar epidermoid cysts mayImmunohistochemical observations develop from eccrine ducts and that HPV (especially HPV 60) may play a role in this development,3,4,10,17 there has been aNormal eccrine sweat gland lack of direct evidence to support this hypothesis.A polyclonal antibody against CEA and a monoclonal antibody HPV 60 was initially identified25,26 in and isolated5 fromAE1 ⁄AE3 (against CKs 10, 14–16, 19 ⁄1–8) stained all the plantar epidermoid cysts with homogeneous intracytoplasmicsecretory, dermal duct and acrosyringeal portions of the ec- inclusion bodies, and was also subsequently found in flatcrine sweat gland. LL002 (against CK14) stained the dermal lesions retaining the appearance of dermal ridges on theirÓ 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967
  6. 6. 966 HPV-associated eccrine epidermoid cyst, K. Egawa et al.surface (ridged warts).16,17 Thus, the clinical morphology of appearance of CKs characteristic of stratified and cornifyingHPV 60-induced lesions also remains unclear. In the present epithelia, indicating a true change in the differentiation of thestudy, using 3DR analysis, it was clearly demonstrated that an middle ear epithelium.12 Interestingly, HPV has also beenHPV 60-associated plantar epidermoid cyst connected with the identified in cholesteatoma.31dermal portion of an eccrine duct. HPV 60 DNA sequences Although the epidermoid cyst analysed with 3DR in thiswere identified not only in the epidermoid cyst but also in study connected with an eccrine dermal duct, the immunore-the acrosyringeal portion of the eccrine duct by DNA–DNA activities for CEA, involucrin and several CKs of the cyst wallin situ hybridization. All the other plantar epidermoid cysts and were not identical to those of normal eccrine dermal ductsridged warts that developed simultaneously on the same but were identical to those of the suprabasal layers of thepatient also harboured HPV 60 DNA sequences, suggesting a epidermis, as observed by Abe et al.,8 Ohnishi and Watanabe9close association between the lesions and HPV 60 infection. A and Yokogawa et al.32 This suggests that the immunoreactivi-tiny keratinous cyst, which might be a precursor of an HPV ties of the palmoplanatar epidermoid cysts may also be an60-associated plantar epidermoid cyst, was also seen just indication of the metaplastic origin of the cysts from eccrinebeneath the acanthotic epidermis of a ridged wart. ducts. In the present case, the eccrine dermal duct with In a previous report, two plantar epidermoid cysts were which the epidermoid cyst connected was hypertrophiedattached to the epidermis and open to the surface in a patient with stratified squamous epithelium and expressed both CEAwith multiple plantar epidermoid cysts harbouring both HPV and involucrin, suggesting a transitional form of the squa-60 DNA sequences and eccrine ducts,3 suggesting that the mous metaplasia of the eccrine duct epithelium.cysts developed from the acrosyringeal or uppermost portions However, as Epstein and Kligman have suggested that kera-of eccrine ducts. As HPV 60 was frequently identified in tinizing cysts may develop from any part of the epithelial sys-palmoplantar epidermoid cysts concomitantly with eccrine tem,33 further studies are still required to determine whetherducts,3,4 we assumed that HPV 60 had a high affinity for the cases in which neither HPV infection nor an associationeccrine duct epithelia and played a role in cyst formation.17 with eccrine ducts has been found in ordinary histological sec-Supporting this idea, recent studies28,29 have suggested that tions reflect a false-negative result or are an indication of epi-papillomaviruses, including HPVs, may target epidermal stem dermal inclusion cysts resulting from the implantation ofcells, which may exist in association with eccrine ducts in the epidermal fragments.human palmoplantar skin.29 In the context of the previous findings and the results of Acknowledgmentsthe present case, we speculate that HPV 60 initially infects theupper parts of the eccrine duct, such as the acrosyringeal epi- We thank Ms Chiemi Shiotsu and Ms Yoshiko Sonoda for tech-thelium, where ridged warts develop, and then migrates into nical assistance and Gyohei Egawa, Haruki Egawa and Motoevarious parts of the dermal portions of the eccrine duct, where Egawa for help in drawing montages of histological pictures.the virus-associated epidermoid cysts develop. It has been revealed that HPV 60-associated palmoplantar Referencesepidermoid cysts occasionally develop in association with pre-ceding blunt or penetrating injuries. The cysts are mainly 1 MacKie RM. Epidermal skin tumours. In: Textbook of Dermatologylocated beneath the weight-bearing areas of the foot, i.e. the (Champion RH, Burton JL, Ebling FJG, eds), 5th edn. Oxford: Blackwell Science, 1992; 1459–504.balls and heels;7 an HPV 60-associated plantar epidermoid cyst 2 Pinkus H. Epidermoid cysts or epidermal inclusion cysts? Arch Der-developed just beneath a plantar wart when the wart was matol 1975; 111:130.being treated with cryotherapy;6 multiple epidermoid cysts 3 Egawa K, Honda Y, Inaba Y et al. Multiple plantar epidermoid cystsharbouring both HPV 60 DNA sequences and eccrine ducts harboring carcinoembryonic antigen and human papillomavirusdeveloped on the sole of a football player.3 DNA sequences. J Am Acad Dermatol 1994; 30:494–6. In the present case, the cryotherapy performed on the pre- 4 Egawa K, Honda Y, Inaba Y et al. Detection of human papillomavi-ceding plantar warts seemed to have a triggering role in the ruses and eccrine ducts in palmoplantar epidermoid cysts. Br J Der- matol 1995; 132:533–42.development of the multiple HPV 60-associated epidermoid 5 Matsukura T, Iwasaki T, Kawashima M. Molecular cloning of a novelcysts. Thus, traumatic injuries and mechanical pressure, which human papillomavirus (type 60) from a plantar epidermoid cysthave long been thought to have a causative role in the implan- with characteristic pathological changes. Virology 1992; 190:561–4.tation of epidermal fragments following cyst formation in the 6 Inaba Y, Egawa K, Muto K, Arao T. Detection of papillomavirusdermis,1 may have a triggering role in the progression of the common antigens in plantar epidermoid cysts. Jpn J Dermatol 1990;HPV 60-infected eccrine duct epithelium to the formation of 100:199–203.the cyst. 7 Egawa K, Inaba Y, Ono T, Arao T. ‘Cystic papilloma’ in humans? Demonstration of human papillomavirus in plantar epidermoid Squamous metaplasia is assumed to be a possible source of cysts. Arch Dermatol 1990; 126:1559–603.cholesteatoma,12,30 which is histologically defined as an epi- 8 Abe H, Ohnishi T, Watanabe S. Does plantar epidermoid cyst withdermoid cyst developing in the middle ear.11 The squamous human papillomavirus infection originate from the eccrine dermalcell metaplasia was immunohistochemically characterized by a duct? Br J Dermatol 1999; 141:161–2.loss of simple epithelial cell-related CKs accompanied by the Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967
  7. 7. HPV-associated eccrine epidermoid cyst, K. Egawa et al. 967 9 Ohnishi T, Watanabe S. Immunohistochemical observation of cyto- between ABC and unlabeled antibody (PAP) procedures. J Histochem keratins in keratinous cysts including plantar epidermoid cyst. Cytochem 1981; 29:577–83. J Cutan Pathol 1999; 26:424–9. 22 Misumi S, Iyama K, Honda Y et al. Differential expression of base-10 Egawa K, Kitasato H, Ono T. A palmar epidermoid cyst, showing ment membrane type-IV collagen a1, a2, a5 and a6 chains among histological features suggestive of eccrine duct origin, developing the histological subtypes of adenoid cystic carcinoma. Virchows Arch after a bee-sting. Br J Dermatol 2000; 143:469–70. 2004; 445:54–62.11 Rosai J. Ear. In: Ackerman’s Surgical Pathology (Rosai L, ed.), 8th edn. 23 Egawa K, Sibasaki Y, de Villiers E-M. Double infection with human St Louis: Mosby, 1996; 2509–17. papillomavirus 1 and human papillomavirus 63 in a single cell of a12 Kuijpers W, Vennix PP, Peters TA, Ramaekers FC. Squamous lesion displaying only an HPV 63-induced cytopathogenic effect. metaplasia of the middle ear epithelium. Acta Otolaryngol 1996; Lab Invest 1993; 69:583–8. 116:293–8. 24 Kawase M, Honda M, Niimura M. Detection of human papilloma-13 Braverman MS, Braverman IM. Three-dimensional reconstructions virus type 60 in plantar epidermoid cysts and verruca plantaris by of objects from serial sections using a microcomputer graphics sys- the in situ hybridization method using digoxigenin labeled probe. tem. J Invest Dermatol 1986; 86:290–4. J Dermatol 1994; 21:709–15.14 Salisbury JR, Whimster WF. Progress in computer-generated three- 25 Egawa K, Ono T, Arao T. Epidermoid cyst of the sole and human dimensional reconstruction. J Pathol 1993; 170:223–7. papillomavirus. Jpn J Dermatol 1987; 97:493–5.15 Honda Y, Egawa K, Baba Y, Ono T. Sweat duct milia—immuno- 26 Kimura S, Sato N, Shigeeki H. A report of two cases of plantar epi- histological analysis of structure and three-dimensional reconstruc- dermoid cyst which have papillomavirus antigen. Hifu-Rinsho 1987; tion. Arch Dermatol Res 1996; 288:133–9. 29:487–91.16 Honda A, Iwasaki T, Sata T et al. Human papillomavirus type 27 Egawa K. New types of human papillomaviruses and intracytoplas- 60-associated plantar wart: ridged wart. Arch Dermatol 1994; mic inclusion bodies, a classification of inclusion warts according 130:1413–17. to clinical features, histology and associated HPV types. Br J Dermatol17 Egawa K, Kasai S, Hattori N et al. A case of a human papillomavirus 1994; 130:158–66. 60-induced wart with clinical appearance of both pigmented and 28 Schmit A, Rochat A, Zeltner R et al. The primary target cells of the ridged warts. Dermatology 1998; 197:268–70. high-risk cottontail rabbit papillomavirus colocalize with hair fol-18 Pennys NS, Nadji M, McKinney EC. Carcinoembryonic antigen pre- licle stem cells. J Virol 1996; 70:1912–22. sent in human eccrine sweat. J Am Acad Dermatol 1981; 29:577–83. 29 Egawa K. Do human papillomaviruses target epidermal stem cells?19 Watanabe S, Ichikawa E, Takanashi S, Takahashi H. Immunohisto- Dermatology 2003; 207:251–4. chemical localization of cytokeratins in normal eccrine glands, with 30 Sade J, Babiacki A, Pinkus G. The metaplastic and congenital origin monoclonal antibodies in routinely processed, formalin-fixed, par- of cholesteatoma. Acta Otolaryngol 1983; 96:119–29. affin-embedded sections. J Am Acad Dermatol 1993; 28:203–12. 31 Bergmann K, Hoppe F, Yukai H et al. Human papillomavirus DNA20 Hudson DL, Weiland KL, Dooley TP et al. Characterization of in cholesteatomas. Int J Cancer 1994; 59:463–6. eight monoclonal antibodies to involucrin. Hybridoma 1992; 11: 32 Yokogawa M, Egawa K, Dabenaka K et al. Multiple palmar epider- 367–79. moid cysts. Dermatology 2002; 205:398–400.21 Hsu H-M, Raine L, Franer H. The use of avidin–biotin peroxidase 33 Epstein WL, Kligman AM. Epithelial cysts in buried human skin. complex (ABC) in immunoperoxidase technique: a comparison Arch Dermatol 1957; 76:437–45.Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp961–967

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